RESUMO
In search of new heterocyclic anticancer agents, a new quinoline-azetidinone hybrid template have been designed, synthesized and screened for their cytotoxic activity against human cancer cell lines such as Hep G2, and Hep 3B by the MTT assay and results were compared with paclitaxel, 5-fluorouracil and doxorubicin. Interestingly, some of the compounds were found significantly active against both cell lines. The compound 6f (IC50=0.04±0.01µM) exhibited potent antiproliferation activity against Hep G2 cell line, and 6j compound (IC50=0.66±0.01µM) demonstrated potent antiproliferation activity against Hep 3B cell line and provide to be more potent as cytotoxic agents than standard drugs. Morphological changes suggest the induction of apoptosis and describe the mechanism of action of these hybrid antitumor agents.
Assuntos
Aminoquinolinas/farmacologia , Antineoplásicos/farmacologia , Azetidinas/farmacologia , Aminoquinolinas/síntese química , Aminoquinolinas/química , Aminoquinolinas/toxicidade , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Azetidinas/síntese química , Azetidinas/química , Azetidinas/toxicidade , Chlorocebus aethiops , Doxorrubicina/farmacologia , Fluoruracila/farmacologia , Células HeLa , Células Hep G2 , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Paclitaxel/farmacologia , Células VeroRESUMO
The effect of the solvent systems water, ethanol (EtOH), propylene glycol (PG) and their binary combinations was studied on the ex vivo permeation profile of the opioid receptor antagonist, naloxone, through rat skin. Fourier transform-infrared (FT-IR) spectroscopic studies were done to investigate the effect of enhancers on the biophysical properties of the stratum corneum (SC), in order to understand the mechanism of permeation enhancement of naloxone by the solvent systems used. The flux of naloxone was found to increase with increasing concentrations of EtOH, upto 66% in water, and PG upto 50% in water. The maximum flux of 32.85 microg cm(-2) h(-1) was found with 33% PG in EtOH. The FT-IR spectra of SC treated with EtOH showed peak broadening at 2920 cm(-1) at all concentrations of EtOH studied indicating that EtOH increases the translational freedom (mobility) of lipid acyl chains. Theoretical blood levels well above the therapeutic concentration of naloxone can be achieved with the solvent system comprising 33% PG in EtOH and hence, provides flexibility in choice of patch size depending on the addiction status of the patient to be treated.
